Preeclampsia activates 15-lipoxygenase and its metabolite 15-hydroxyeicosatetraenoic acid enhances constriction in umbilical arteries

Prostaglandins Leukot Essent Fatty Acids. 2012 Jan-Feb;86(1-2):79-84. doi: 10.1016/j.plefa.2011.10.006. Epub 2011 Nov 10.

Abstract

Objective: To compare the differential expression of 15-lipoxygenase (15-LO) isoenzymes, 15-LO-1 and 15-LO-2 in preeclampsia (PE), and normal pregnancy and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) on the vasoconstriction of human umbilical artery (HUA) rings.

Study design: We performed western blotting and isometric tension studies and t-test analysis on data from 6 women with normal pregnancy and 8 women with PE.

Results: Expressions of 15-LO-1 and 15-LO-2 in placentas and HUA rings in PE increased more than that in normal groups (P<0.01). 15-HETE increased HUA rings tension in a dose-dependence manner, which were significantly greater in PE than in normal pregnant controls (P<0.01). However, the constriction of HUA rings was completely eliminated by 2-aminoethoxydiphenyl borate (2-APB) in both normal pregnancy and PE (P<0.01) and attenuated partly by nifedipine in dose-dependence in normal pregnancy (10(-8)mol/L P>0.05; 10(-7), 10(-6)mol/L P<0.05) and in PE (P<0.01).

Conclusion: PE upregulates 15-LO pathway via 15-HETE, which increased intercellular calcium level to cause constriction of HUA rings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Enzyme Activation / physiology
  • Female
  • Gestational Age
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism*
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • In Vitro Techniques
  • Maternal Age
  • Nifedipine / pharmacology
  • Placenta / blood supply
  • Placenta / metabolism
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology*
  • Pregnancy
  • Umbilical Arteries / drug effects
  • Umbilical Arteries / metabolism
  • Umbilical Arteries / physiology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasodilator Agents / pharmacology

Substances

  • Hydroxyeicosatetraenoic Acids
  • Vasodilator Agents
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • ALOX15B protein, human
  • Arachidonate 15-Lipoxygenase
  • Nifedipine